CA2781228A1 - Manganese chelates and their use as contrast agents in magnetic resonance imaging (mri) - Google Patents
Manganese chelates and their use as contrast agents in magnetic resonance imaging (mri) Download PDFInfo
- Publication number
- CA2781228A1 CA2781228A1 CA2781228A CA2781228A CA2781228A1 CA 2781228 A1 CA2781228 A1 CA 2781228A1 CA 2781228 A CA2781228 A CA 2781228A CA 2781228 A CA2781228 A CA 2781228A CA 2781228 A1 CA2781228 A1 CA 2781228A1
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- Prior art keywords
- compound according
- linker
- compound
- alkyl
- added
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000002872 contrast media Substances 0.000 title claims abstract description 30
- 239000011572 manganese Substances 0.000 title abstract description 24
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 title abstract description 17
- 238000002595 magnetic resonance imaging Methods 0.000 title abstract description 14
- 229910052748 manganese Inorganic materials 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 82
- 125000005647 linker group Chemical group 0.000 claims description 24
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 13
- 238000003384 imaging method Methods 0.000 claims description 9
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 9
- 239000000412 dendrimer Substances 0.000 claims description 8
- 229920000736 dendritic polymer Polymers 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 229920001184 polypeptide Polymers 0.000 claims description 6
- 102000004169 proteins and genes Human genes 0.000 claims description 6
- 108090000623 proteins and genes Proteins 0.000 claims description 6
- 239000000816 peptidomimetic Substances 0.000 claims description 5
- 229920000768 polyamine Polymers 0.000 claims description 5
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
- 150000002634 lipophilic molecules Chemical class 0.000 claims description 4
- 239000002105 nanoparticle Substances 0.000 claims description 4
- 229920005615 natural polymer Polymers 0.000 claims description 4
- 229920001059 synthetic polymer Polymers 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 3
- 238000001228 spectrum Methods 0.000 claims description 3
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 150000001720 carbohydrates Chemical class 0.000 claims description 2
- 239000000032 diagnostic agent Substances 0.000 claims description 2
- 229940039227 diagnostic agent Drugs 0.000 claims description 2
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims description 2
- 229960000367 inositol Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 239000000047 product Substances 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 230000005298 paramagnetic effect Effects 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- 239000002002 slurry Substances 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- -1 manganese(II) ions Chemical class 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 150000002500 ions Chemical class 0.000 description 12
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 12
- 238000011445 neoadjuvant hormone therapy Methods 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000013522 chelant Substances 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 229910052688 Gadolinium Inorganic materials 0.000 description 4
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 4
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 4
- 239000011565 manganese chloride Substances 0.000 description 4
- 235000002867 manganese chloride Nutrition 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000283891 Kobus Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000002051 biphasic effect Effects 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- IWQNFYRJSVJWQA-UHFFFAOYSA-N 2,6-bis(chloromethyl)pyridine Chemical compound ClCC1=CC=CC(CCl)=N1 IWQNFYRJSVJWQA-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 229910018663 Mn O Inorganic materials 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229960005069 calcium Drugs 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000007894 caplet Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 239000013580 millipore water Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 2
- 125000006248 tosyl amino group Chemical group [H]N(*)S(=O)(=O)C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- 125000005490 tosylate group Chemical group 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 1
- VBNWSEVVMYMVLC-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonylaziridine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CC1 VBNWSEVVMYMVLC-UHFFFAOYSA-N 0.000 description 1
- ZJUCFUOCTOGYEE-UHFFFAOYSA-N 2,6-bis(chloromethyl)pyridin-4-amine Chemical compound NC1=CC(CCl)=NC(CCl)=C1 ZJUCFUOCTOGYEE-UHFFFAOYSA-N 0.000 description 1
- RZESKRXOCXWCFX-UHFFFAOYSA-N 2-[bis[2-[carboxymethyl-[2-(methylamino)-2-oxoethyl]amino]ethyl]amino]acetic acid Chemical compound CNC(=O)CN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC(=O)NC RZESKRXOCXWCFX-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- LNMUPMQUMCDOKO-UHFFFAOYSA-N 3,6,9,15-tetrazabicyclo[9.3.1]pentadeca-1(15),11,13-triene Chemical compound C1NCCNCCNCC2=CC=CC1=N2 LNMUPMQUMCDOKO-UHFFFAOYSA-N 0.000 description 1
- IHEBMGYEECNNJH-UHFFFAOYSA-N 4-aminopyridine-2,6-dicarboxylic acid Chemical compound NC1=CC(C(O)=O)=NC(C(O)=O)=C1 IHEBMGYEECNNJH-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
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- 238000000944 Soxhlet extraction Methods 0.000 description 1
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- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- DCTUDWALVLSNML-UHFFFAOYSA-N [4-amino-6-(hydroxymethyl)pyridin-2-yl]methanol Chemical compound NC1=CC(CO)=NC(CO)=C1 DCTUDWALVLSNML-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
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- 239000008365 aqueous carrier Substances 0.000 description 1
- DLGYNVMUCSTYDQ-UHFFFAOYSA-N azane;pyridine Chemical compound N.C1=CC=NC=C1 DLGYNVMUCSTYDQ-UHFFFAOYSA-N 0.000 description 1
- VXPZSDUXKPVHJC-UHFFFAOYSA-N benzene-1,2,3-tricarbonyl chloride Chemical compound ClC(=O)C1=CC=CC(C(Cl)=O)=C1C(Cl)=O VXPZSDUXKPVHJC-UHFFFAOYSA-N 0.000 description 1
- WXWQVSOHWXJBDF-UHFFFAOYSA-N benzene-1,3,5-tricarboxamide Chemical compound NC(=O)C1=CC(C(N)=O)=CC(C(N)=O)=C1 WXWQVSOHWXJBDF-UHFFFAOYSA-N 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
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- 239000011692 calcium ascorbate Substances 0.000 description 1
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- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
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- BLORRZQTHNGFTI-ZZMNMWMASA-L calcium-L-ascorbate Chemical compound [Ca+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] BLORRZQTHNGFTI-ZZMNMWMASA-L 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- BHRQIJRLOVHRKH-UHFFFAOYSA-L calcium;2-[bis[2-[bis(carboxylatomethyl)amino]ethyl]amino]acetate;hydron Chemical compound [Ca+2].OC(=O)CN(CC(O)=O)CCN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O BHRQIJRLOVHRKH-UHFFFAOYSA-L 0.000 description 1
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- MZTSUWWTESDXNW-UHFFFAOYSA-N dimethyl 4-aminopyridine-2,6-dicarboxylate Chemical compound COC(=O)C1=CC(N)=CC(C(=O)OC)=N1 MZTSUWWTESDXNW-UHFFFAOYSA-N 0.000 description 1
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- WTFXARWRTYJXII-UHFFFAOYSA-N iron(2+);iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+2].[Fe+3].[Fe+3] WTFXARWRTYJXII-UHFFFAOYSA-N 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
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- 210000004185 liver Anatomy 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
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- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
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- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- QEUGACRMCVLHHQ-UHFFFAOYSA-N n-[2-[2-[bis[2-[bis[2-[(4-methylphenyl)sulfonylamino]ethyl]amino]ethyl]amino]ethyl-[2-[(4-methylphenyl)sulfonylamino]ethyl]amino]ethyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NCCN(CCN(CCN(CCNS(=O)(=O)C=1C=CC(C)=CC=1)CCNS(=O)(=O)C=1C=CC(C)=CC=1)CCN(CCNS(=O)(=O)C=1C=CC(C)=CC=1)CCNS(=O)(=O)C=1C=CC(C)=CC=1)CCNS(=O)(=O)C1=CC=C(C)C=C1 QEUGACRMCVLHHQ-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 229940086542 triethylamine Drugs 0.000 description 1
- MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical compound NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 description 1
- 229940073585 tromethamine hydrochloride Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
- A61K49/106—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/12—Macromolecular compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic Table
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Radiology & Medical Imaging (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO20093555A NO331773B1 (no) | 2009-12-18 | 2009-12-18 | Mangankelater, sammensetninger omfattende slike og anvendelse av disse som kontrastmidler for magnettomografi (MR) |
| NO20093555 | 2009-12-18 | ||
| PCT/EP2010/070029 WO2011073371A1 (en) | 2009-12-18 | 2010-12-17 | Manganese chelates and their use as contrast agents in magnetic resonance imaging (mri) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2781228A1 true CA2781228A1 (en) | 2011-06-23 |
Family
ID=43770529
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2781228A Abandoned CA2781228A1 (en) | 2009-12-18 | 2010-12-17 | Manganese chelates and their use as contrast agents in magnetic resonance imaging (mri) |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US9486544B2 (enExample) |
| EP (1) | EP2512524B1 (enExample) |
| JP (1) | JP5879268B2 (enExample) |
| KR (1) | KR101860160B1 (enExample) |
| CN (1) | CN102639152B (enExample) |
| AU (1) | AU2010332760B2 (enExample) |
| BR (1) | BR112012013761A2 (enExample) |
| CA (1) | CA2781228A1 (enExample) |
| DK (1) | DK2512524T3 (enExample) |
| ES (1) | ES2606165T3 (enExample) |
| HR (1) | HRP20161627T1 (enExample) |
| HU (1) | HUE032152T2 (enExample) |
| LT (1) | LT2512524T (enExample) |
| MX (1) | MX2012007041A (enExample) |
| NO (1) | NO331773B1 (enExample) |
| PL (1) | PL2512524T3 (enExample) |
| PT (1) | PT2512524T (enExample) |
| RU (1) | RU2561718C2 (enExample) |
| WO (1) | WO2011073371A1 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2988756T4 (da) | 2013-04-26 | 2022-08-08 | Guerbet Sa | Formulering af kontraststof og dertil knyttet fremstillingsfremgangsmåde |
| EP3101012A1 (en) | 2015-06-04 | 2016-12-07 | Bayer Pharma Aktiengesellschaft | New gadolinium chelate compounds for use in magnetic resonance imaging |
| EP3380484A1 (en) | 2015-11-26 | 2018-10-03 | Debreceni Egyetem | New 6-oxa-3,9, 15-triaza-bicyclo[9.3.1 ]pentadec a- 1 ( 14), 1 1 ( 15), 12-triene derivatives based compounds and their application as ligands of essential metal ion based mri and 52mn based pet contrast agents |
| WO2017089847A1 (en) | 2015-11-26 | 2017-06-01 | Debreceni Egyetem | New 3,6,9, 15-tetraaza-bicyclo [9.3.1 ]pentadeca- 1(14), 11(15), 12-triene based compounds and their application as ligands of essential metal ion based mri and 52mn based pet contrast agents |
| US10968224B2 (en) | 2015-11-26 | 2021-04-06 | Debreceni Egyetem | 2,11-diaza-[3.3](2,6)pyridinophane compounds and their application as ligands of essential metal ion based MRI contrast agents and 52MN based PET contrast agents |
| GB201610738D0 (en) * | 2016-06-20 | 2016-08-03 | Ge Healthcare As | Chelate compounds |
| WO2018096082A1 (en) | 2016-11-28 | 2018-05-31 | Bayer Pharma Aktiengesellschaft | High relaxivity gadolinium chelate compounds for use in magnetic resonance imaging |
| PL3558394T3 (pl) * | 2016-12-21 | 2020-11-16 | Ge Healthcare As | Oparte na tetraazabicyklo-makrocyklu związki chelatowe manganu odpowiednie jako środki do obrazowania metodą MRI |
| EP3728168B1 (en) * | 2017-12-20 | 2022-03-30 | General Electric Company | Anionic chelate compounds |
| MY208484A (en) | 2018-11-23 | 2025-05-13 | Bayer Pharma AG | Formulation of contrast media and process of preparation thereof |
| CN111233982B (zh) * | 2018-11-28 | 2023-03-03 | 深圳先进技术研究院 | 一种小分子蛋白质及其应用 |
| HUE069750T2 (hu) | 2019-09-03 | 2025-04-28 | Ge Healthcare As | Mangán-kelát izomerek |
| CN114874214B (zh) * | 2022-05-31 | 2023-03-21 | 南京航空航天大学 | 可偶联巯基的双功能大环螯合剂衍生物及其制备方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU608759B2 (en) | 1986-08-04 | 1991-04-18 | Amersham Health Salutar Inc | NMR imaging with paramagnetic polyvalents metal salts of poly-(acid-alkylene-amido)-alkanes |
| DE3640708C2 (de) | 1986-11-28 | 1995-05-18 | Schering Ag | Verbesserte metallhaltige Pharmazeutika |
| US5334371A (en) * | 1988-07-20 | 1994-08-02 | Schering Aktiengesellschaft | Marcocyclic polyaza bicyclo compounds containing 5 or 6 membered rings, and method for MRI |
| DE68908185T2 (de) | 1988-09-27 | 1993-11-25 | Nycomed Salutar Inc | Chelat-zusammensetzung. |
| ES2145041T3 (es) * | 1991-12-10 | 2000-07-01 | Dow Chemical Co | Complejos de acidos biciclopoliazamacrociclocarboxilicos, sus conjugados, preparacion y uso como agentes de contraste. |
| ZA929576B (en) * | 1991-12-10 | 1994-06-10 | Dow Chemical Co | Bicyclopolyazamacrocyclophosphonic acids their complexes and conjugates for use as contrast agents and processes for their preparation |
| US5428139A (en) * | 1991-12-10 | 1995-06-27 | The Dow Chemical Company | Bicyclopolyazamacrocyclophosphonic acid complexes for use as radiopharmaceuticals |
| FI933506A7 (fi) * | 1993-05-06 | 1994-11-07 | Dow Global Technologies Inc | Bisyklopolyatsamakrosyklokarboksyylihappokomplekseja, niiden konjugaat teja, menetelmä niiden valmistamiseksi ja käyttö varjoaineina |
| FR2836916B1 (fr) * | 2002-03-05 | 2004-06-11 | Guerbet Sa | Oligomeres de chelates de gadolinium, leur application comme produits de contraste en imagerie par resonance magnetique et leurs intermediaires de synthese |
| FR2856689A1 (fr) * | 2003-06-25 | 2004-12-31 | Guerbet Sa | Composes specifiques a forte relaxivite |
| US20080305049A1 (en) | 2005-01-31 | 2008-12-11 | Hadassa Degani | Mri Contrast Agents for Diagnosis and Prognosis of Tumors |
-
2009
- 2009-12-18 NO NO20093555A patent/NO331773B1/no unknown
-
2010
- 2010-12-17 CN CN201080056567.0A patent/CN102639152B/zh active Active
- 2010-12-17 MX MX2012007041A patent/MX2012007041A/es not_active Application Discontinuation
- 2010-12-17 ES ES10805224.2T patent/ES2606165T3/es active Active
- 2010-12-17 WO PCT/EP2010/070029 patent/WO2011073371A1/en not_active Ceased
- 2010-12-17 RU RU2012124266/04A patent/RU2561718C2/ru not_active IP Right Cessation
- 2010-12-17 AU AU2010332760A patent/AU2010332760B2/en not_active Ceased
- 2010-12-17 EP EP10805224.2A patent/EP2512524B1/en active Active
- 2010-12-17 KR KR1020127015488A patent/KR101860160B1/ko not_active Expired - Fee Related
- 2010-12-17 DK DK10805224.2T patent/DK2512524T3/en active
- 2010-12-17 US US13/510,064 patent/US9486544B2/en active Active
- 2010-12-17 HU HUE10805224A patent/HUE032152T2/en unknown
- 2010-12-17 HR HRP20161627TT patent/HRP20161627T1/hr unknown
- 2010-12-17 PL PL10805224T patent/PL2512524T3/pl unknown
- 2010-12-17 CA CA2781228A patent/CA2781228A1/en not_active Abandoned
- 2010-12-17 LT LTEP10805224.2T patent/LT2512524T/lt unknown
- 2010-12-17 PT PT108052242T patent/PT2512524T/pt unknown
- 2010-12-17 JP JP2012543778A patent/JP5879268B2/ja active Active
- 2010-12-17 BR BR112012013761A patent/BR112012013761A2/pt not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| JP2013514329A (ja) | 2013-04-25 |
| HUE032152T2 (en) | 2017-09-28 |
| MX2012007041A (es) | 2012-07-20 |
| PT2512524T (pt) | 2016-12-15 |
| HRP20161627T1 (hr) | 2017-01-13 |
| NO331773B1 (no) | 2012-03-26 |
| US20120244081A1 (en) | 2012-09-27 |
| RU2561718C2 (ru) | 2015-09-10 |
| ES2606165T3 (es) | 2017-03-23 |
| CN102639152B (zh) | 2015-11-25 |
| JP5879268B2 (ja) | 2016-03-08 |
| CN102639152A (zh) | 2012-08-15 |
| AU2010332760A1 (en) | 2012-06-07 |
| KR20120109505A (ko) | 2012-10-08 |
| AU2010332760B2 (en) | 2016-01-07 |
| PL2512524T3 (pl) | 2017-08-31 |
| NO20093555A1 (no) | 2011-06-20 |
| DK2512524T3 (en) | 2017-01-09 |
| WO2011073371A1 (en) | 2011-06-23 |
| BR112012013761A2 (pt) | 2016-04-26 |
| LT2512524T (lt) | 2016-12-12 |
| EP2512524B1 (en) | 2016-10-05 |
| EP2512524A1 (en) | 2012-10-24 |
| US9486544B2 (en) | 2016-11-08 |
| KR101860160B1 (ko) | 2018-05-21 |
| RU2012124266A (ru) | 2014-01-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20141217 |